ABSTRACT
[This corrects the article DOI: 10.3389/fchem.2024.1378233.].
ABSTRACT
Introduction: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer still lacking effective treatment options. Chemotherapy in combination with immunotherapy can restrict tumor progression and repolarize the tumor microenvironment towards an anti-tumor milieu, improving clinical outcome in TNBC patients. The chemotherapeutic drug paclitaxel has been shown to induce immunogenic cell death (ICD), whereas inhibitors of the indoleamine 2,3- dioxygenase 1 (IDO1) enzyme, whose expression is shared in immune regulatory and tumor cells, have been revealed to enhance the anti-tumor immune response. However, poor bioavailability and pharmacokinetics, off-target effects and hurdles in achieving therapeutic drug concentrations at the target tissue often limit the effectiveness of combination therapies. Methods: This work describes the development of novel biomimetic and carrier-free nanobinders (NBs) loaded with both paclitaxel and the IDO1 inhibitor NLG919 in the form of bioresponsive and biomimetic prodrugs. A fine tuning of the preparation conditions allowed to identify NB@5 as the most suitable nanoformulation in terms of reproducibility, stability and in vitro effectiveness. Results and discussion: Our data show that NB@5 effectively binds to HSA in cell-free experiments, demonstrating its protective role in the controlled release of drugs and suggesting the potential to exploit the protein as the endogenous vehicle for targeted delivery to the tumor site. Our study successfully proves that the drugs encapsulated within the NBs are preferentially released under the altered redox conditions commonly found in the tumor microenvironment, thereby inducing cell death, promoting ICD, and inhibiting IDO1.
ABSTRACT
Diabetic kidney disease (DKD) is a major cause of morbidity and mortality in individuals with type 2 diabetes mellitus (T2DM). The aim of this study was to investigate whether albumin structural alterations correlate with DKD severity and evaluate whether native and reduced albumin concentrations could complement the diagnosis of DKD. To this end, one hundred and seventeen T2DM patients without (n = 42) and with (n = 75) DKD (DKD I-III upon KDIGO classification) were evaluated; the total albumin concentration (tHA) was quantified by a bromocresol green assay, while structural alterations were profiled via liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The concentrations of native albumin (eHA, effective albumin) and reduced albumin (rHA) were subsequently assessed. The HRMS analyses revealed a reduced relative amount of native albumin in DKD patients along with an increased abundance of altered forms, especially those bearing oxidative modifications. Accordingly, both eHA and rHA values varied during the stages of progressive renal failure, and these alterations were dose-dependently correlated with renal dysfunction. A ROC curve analysis revealed a significantly greater sensitivity and specificity of eHA and rHA than of tHA for diagnosing DKD. Importantly, according to the multivariate logistic regression analysis, the eHA was identified as an independent predictor of DKD.
